The research proposed has as an overall objective the understanding of the biochemical basis for the mechanisms in lung which guarantee the biosynthetic specificity required for the production of the unique functional lecithin, dipalmitoylphosphatidylcholine, the primary surface-active agent of the pulmonary surfactant complex. Central to adequate resolution of this question is further information on the biochemical and enzymological properties of the enzyme systems which are potentially involved. Needed is information on tissue multiplicity, subcellular distribution, reaction specificity and factors which affect and modify expression of actual enzyme activity. We have begun such studies on CDP-choline: diglyceride cholinephosphotransferase, the enzyme considered responsible for most lecithin biosynthesis in the adult rabbit lung. We have evidence for: 1) multiple forms of this enzyme having different subcellular locations, 2) factors not previously appreciated which can dramatically influence the amounts of activity measured by previously employed assays, and 3) an apparent lack of marked specificity for the diglycerides used in the production of lecithin. In light of these new findings, it is proposed to reexamine the changes in activity of this enzyme in fetal rabbit lung during gestation and corticosteroid induction. Previous apparent contradictory conclusions may be resolved in light of our new findings. Further, we propsed to extend similar investigations to enzymes of other potential pathways for de novo biosynthesis as welll as to the phospholipase A activity necessary for the pathways proposed for restructuring existing non-surfactant lecithin to the surface-active form.